Vasküler Yaşlanmada Bağırsak Mikrobiyotası Kaynaklı Metabolitlerin Entegrasyonu İçin Sistem Biyolojisi Temelli Hesaplamalı Bir Çerçeve: MCAS Modeli

Yıl 2026, Cilt: 42 Sayı: 1 , - , 23.03.2026

Erkan Özbay , Serkan Örücü , Sami Karagöz , Sait Ramazan Gülbay , Bülent Işık

https://izlik.org/JA99TH87RW

Öz

Yaşlanma, enerji metabolizmasındaki, epigenomik düzenlemedeki ve kronik düşük dereceli inflamasyondaki birbiriyle bağlantılı değişiklikler tarafından şekillendirilen çok faktörlü bir süreçtir. Burada, mikrobiyom kaynaklı metabolitleri vasküler yaşlanma ile ilişkili biyolojik özelliklerle sistem biyolojisi yaklaşımını kullanarak bütünleştirmek için çok katmanlı bir hesaplamalı model tanımlanmaktadır. Mikrobiyal, metabolik ve epigenomik bileşenleri birleştiren bileşik bir indeks oluşturulmuş ve herkese açık veri kümelerine dayanarak analiz edilmiştir. İç içe geçmiş çapraz doğrulama şeması içinde uygulanan L2-düzenlileştirilmiş bir lojistik regresyon modeli, genel model davranışını değerlendirmek için kullanılmıştır. Entegre model, ortalama AUC değeri 0.893 (95% GA: 0.787-0.959), PR-AUC değeri 0.913 ve Brier skoru 0.147 olmak üzere tutarlı biçimde kararlı bir performans göstermiştir. Ablasyon analizleri ayrıca mikrobiyal özelliklerin model ayrım gücüne en güçlü katkıyı sağladığını, metabolik ve epigenomik bileşenlerin ise esas olarak model kararlılığına katkıda bulunduğunu göstermiştir. Tüm bunlar birlikte ele alındığında, bu model mikrobiyota ile ilişkili biyolojik örüntülerin vasküler yaşlanma ile ilişkili olarak yorumlanması için bütünleştirici bir hesaplamalı yaklaşım sunmaktadır.

Anahtar Kelimeler

Bağırsak Mikrobiyotası , Vasküler Yaşlanma , Sistem Biyolojisi , Trimetilamin N-Oksit , Kısa Zincirli Yağ Asitleri

A Systems Biology-Based Computational Framework for Integrating Gut Microbiota-Derived Metabolites in Vascular Aging: The MCAS Model

https://izlik.org/JA99TH87RW

Öz

Aging is a multifactorial process that is shaped by interconnected alterations in energy metabolism, epigenomic regulation, and chronic low-grade inflammation. Here, a multilayered computational model is described to integrate microbiome-derived metabolites with vascular aging-related biological features using a systems biology approach. A composite index that combines microbial, metabolic, and epigenomic components was constructed and analyzed based on publicly available datasets. An L2-regularized logistic regression model implemented with in a nested cross-validation scheme was employed to evaluate overall model behavior. The integrated model demonstrated consistently stable performance, with a mean AUC of 0.893 (95% CI: 0.787-0.959), a PR-AUC of 0.913, and a Brier score of 0.147. Ablation analyses further showed that microbial features contributed most strongly to model discrimination, while metabolic and epigenomic components mainly contributed to model stability. Taken together, this model provides an integrative computational approach for interpreting microbiota-associated biological patterns in relation to vascular aging.

Anahtar Kelimeler

Gut microbiota , Vascular Aging , Systems Biology , Trimethylamine N-Oxide , Short-Chain Fatty Acids

Etik Beyan

This study received approval from the Medicine Local Scientific Medical Research Ethics Committee (date: 09 December 2025; approval no: 26-2025/23). The study was conducted in accordance with applicable ethical standards and the principles of the Declaration of Helsinki. As the analyses were based solely on previously collected, anonymized, and publicly available datasets, informed consent was not required.

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